Early Onset Alzheimer Disease (EOAD) and Late Onset Alzheimer Disease (LOAD) share the same pathological features and are considered the same disorder affecting people at different ages, under 65 ...years for EOAD, over 65 years for LOAD. Whether the different pathological burden could influence also synaptic plasticity mechanisms has never been addressed yet. The aim of our study is to investigate the neurophysiological characteristics of these patients through transcranial magnetic stimulation protocols, comparing with two control groups, respectively old healthy and young healthy age-matched subjects. To verify this hypothesis we evaluated a group of 22 sporadic EOAD and 33 LOAD for plasticity induction of LTP/LTD-like effects using respectively intermittent TBS (iTBS) or continuous TBS (cTBS). Central cholinergic activity was evaluated by means of short afferent inhibition (SAI) protocol. Patients, both EOAD and LOAD, showed an impairment of LTP mechanisms while healthy controls, showed a normal profile of cortical plasticity. SAI protocol results show a positive correlation between SAI dysfunction and aging, reflecting acetylcholine role in aging. The central cholinergic pathway seems to be affected more by age than by the disease process itself. LTP mechanisms are altered in AD patients despite the age, thus representing a reliable marker of disease.
Background. Recently, increased interest has been shown in Theory of Mind (ToM) abilities of individuals with severe acquired brain injury (sABI). ToM impairment following sABI can be associated with ...altered executive functioning and/or with difficulty in decoding and elaborating emotions. Two main theoretical models have been proposed to explain the mechanisms underlying ToM in the general population: Theory Theory and Simulation Theory. This review presents and discusses the literature on ToM abilities in individuals with sABI by examining whether they sustain the applicability of the Theory Theory and/or Simulation Theory to account for ToM deficits in this clinical population. We found 32 papers that are directly aimed at investigating ToM in sABI. Results did not show the univocal predominance of one model with respect to the other in explaining ToM deficits in sABI. We hypothesised that ToM processes could be explained by coinvolvement of the two models, i.e., according to personal experience, cognitive features, or the emotional resources of the persons with sABI.
Early Onset Alzheimer Disease (EOAD) and Late Onset Alzheimer Disease (LOAD) share the same pathological features and are considered the same disorder affecting people at different ages, under 65 ...years for EOAD, over 65 years for LOAD. Whether the different pathological burden could influence also synaptic plasticity mechanisms has never been addressed yet. The aim of our study is to investigate the neurophysiological characteristics of these patients through transcranial magnetic stimulation protocols, comparing with two control groups, respectively old healthy and young healthy age-matched subjects. To verify this hypothesis we evaluated a group of 22 sporadic EOAD and 33 LOAD for plasticity induction of LTP/LTD-like effects using respectively intermittent TBS (iTBS) or continuous TBS (cTBS). Central cholinergic activity was evaluated by means of short afferent inhibition (SAI) protocol. Patients, both EOAD and LOAD, showed an impairment of LTP mechanisms while healthy controls, showed a normal profile of cortical plasticity. SAI protocol results show a positive correlation between SAI dysfunction and aging, reflecting acetylcholine role in aging. The central cholinergic pathway seems to be affected more by age than by the disease process itself. LTP mechanisms are altered in AD patients despite the age, thus representing a reliable marker of disease.
The neural mechanisms and circuitry involved in levodopa-induced dyskinesia are unclear. Using repetitive transcranial magnetic stimulation (rTMS) over the supplementary motor area (SMA) in a group ...of patients with advanced Parkinson disease, the authors investigated whether modulation of SMA excitability may result in a modification of a dyskinetic state induced by continuous apomorphine infusion. rTMS at 1 Hz was observed to markedly reduce drug-induced dyskinesias, whereas 5-Hz rTMS induced a slight but not significant increase.
In todays aging society, many people require mobility assistance, that can be provided by robotized assistive wheelchairs with a certain degree of autonomy when manual control is unfeasible due to ...disability.
Robot wheelchairs, though, are not supposed to be completely in control because lack of human intervention may lead to loss of residual capabilities and frustration. Most of these systems rely on shared control, which typically consists of swapping control from human to robot when needed. However, this means that persons never deal with situations they find difficult. We propose a new shared control approach to allow constant cooperation between humans and robots, so that assistance may be adapted to the user’s skills. Our proposal is based on the reactive navigation paradigm, where robot and human commands become different goals in a Potential Field. Our main novelty is that human and robot attractors are weighted by their respective local efficiencies at each time instant. This produces an emergent behavior that combines both inputs in an efficient, safe and smooth way and is dynamically adapted to the user’s needs. The proposed control scheme has been successfully tested at hospital Fondazione Santa Lucia (FSL) in Rome with several volunteers presenting different disabilities.
Introduction Mechanisms of cortical plasticity have been widely investigated in Alzheimer’s disease (AD) patients with TMS protocols, showing a clear impairment of Long-Term Potentiation (LTP) ...cortical-like plasticity and a relative sparing of Long Term Depression (LTD) mechanisms. Recently a new TMS protocol, investigating the connections between posterior parietal cortex (PPC) and primary motor cortex (M1), elicited in a bidirectional way LTP and LTD effects. Objective We investigated mechanisms of spike-timing dependent plasticity in AD patients and the effects of the modulation of PPC-M1 pathway on cholinergic transmission, greatly impaired in AD patients. Material and methods Twelve AD patients and eight age-matched healthy subjects (HS) were evaluated. We used bifocal TMS to repeatedly activate the connections between the PPC and M1 of the left-dominant hemisphere. PPC TMS preceded or followed the M1 stimulation by 5 ms, respectively PAS +5 and PAS −5. To best activate the ipsilateral PPC-M1 connection, the conditioning stimulus was applied over the left PPC at an intensity of 90% of the ipsilateral resting motor threshold. For the PAS protocol, 100 pairs of stimuli were continuously delivered at a rate of 0.2 Hz for ∼8.3 min. Motor evoked potentials and central cholinergic way, evaluated with Short-latency afferent inhibition (SAI) protocol, were evaluated before and after PAS (+5 or −5) protocol. Results as expected HS showed an LTP-like cortical plasticity following PAS −5 protocol and an LTD-like cortical plasticity after PAS +5 protocol, while AD patients did not show any modification of the amplitude of MEP after repeated activation of PPC-M1 connections. As compared to HS, AD patients showed worst SAI values. Interestingly, after PAS +5 protocol, in AD patients SAI levels were restored. Conclusions The data here presented confirm that in AD patients there is an altered cortical plasticity. The central cholinergic way is altered in AD patients, but after the application of PAS +5 protocol his levels are restored, suggesting a possible role of PPC-M1 pathway on modulation of this inhibitory intracortical circuit. PAS protocol is able to investigate the mechanisms of altered cortical plasticity in AD patients. Central cholinergic transmission can be modulated by stimulation of PPC-M1 connections.
Introduction Several studies have already shown that transcranial direct current stimulation (tDCS) is an useful tool to enhance recovery in aphasia. However, no reports to date have investigated ...functional connectivity changes on cortical activity due to tDCS language treatment. Objectives The present study explored whether bilateral tDCS over the frontal regions would improve language performance in a group of aphasic patients. We also wanted to assess the impact of dual tDCS language treatment on functional connectivity reorganization through rs-fMRI. Materials & methods Nine aphasic persons with articulatory disorders underwent an intensive language therapy in two different conditions: bilateral anodic stimulation over the left Broca’s area and cathodic contralesional stimulation over the right homologue of Broca’s area and a sham condition. The language treatment lasted three weeks (Monday to Friday – fifteen daily sessions). In all patients, language measures were collected before (T0) and at the end of treatment (T15). Before and after each treatment condition (real vs.sham), each subject underwent a resting state fMRI (rsfMRI). Results Results showed that, after real stimulation, patients exhibited the greatest recovery not only in terms of better accuracy in articulating the treated stimuli but also for untreated items on different tasks of the language test (picture description, noun and verb naming, word repetition, word reading). Moreover, while after the sham condition connectivity changes were confined into the right brain hemisphere, bilateral stimulation yielded to stronger functional connectivity increase in the left hemisphere. Conclusion In conclusion, our data provide converging evidence from behavioural and functional imaging data that bilateral tDCS determines functional connectivity changes into the lesioned hemisphere enhancing language recovery process in stroke patients.
The potential effects of APOE isoforms on lipid metabolism, cell signaling, and neurotoxicity in the central nervous system have the potential to influence Alzheimer’s disease (AD). Several studies ...demonstrate that APOE E4 allele associates not only with AD risk and a lower age onset, but also with faster cognitive decline and greater cerebral atrophy, suggesting a key role of this polymorphism in modulating both disease risk and clinical outcome. In the current study, we investigated the correlation between cognitive decline, motor cortical plasticity and cerebrospinal fluid (CSF) biomarkers profile of AD patients divided by APOE polymorphism in E4 allele carriers (E4) and homozygous E3 carriers. A monophasic Magstim 200 device was used to deliver intermitted/continuous theta burst stimulation (iTBS/cTBS) protocols. ELISA was used for determination of CSF protein concentrations. Forty-one AD patients underwent lumbar puncture for CSF withdrawal, blood screening for APOE polymorphism, neurostimulation protocols applied over the primary motor cortex and repeated mini mental state examination (MMSE) at 6-, 12- and 18-months. No difference was found in CSF biomarkers profile within the APOE variants group. Conversely iTBS after effects were significantly reduced in E3 AD in comparison with E4 AD patients. MMSE progression, evaluated as delta between 18-month and baseline MMSE score (delta-MMSE) was higher, although not significantly, for E4 AD patients. Correlation analyses revealed that the individual amount of iTBS induced plasticity did correlate with delta-MMSE and total Tau (t-Tau), showing that a less pronounced LTP-like plasticity and higher t-Tau CSF levels were associated with a higher delta-MMSE. Finally a multivariate analysis showed that APOE polymorphism and LTP-like plasticity, but not t-Tau levels are independently able to predict delta-MMSE in AD patients. These findings demonstrate that cortical plasticity impairment in AD patients is significantly different according to APOE variants. Moreover APOE polymorphism and LTP-like plasticity are both independently associated with clinical progression in AD patients. APOE variants show different level of cortical plasticity and are independently associated with clinical progression in AD patients.
ischaemic stroke has been associated with an impairment of cardiac autonomic balance. The aim of this study was to assess the impact of cardiac autonomic derangement on functional outcome after a ...rehabilitation program in patients with recent ischaemic stroke. The study population included 85 consecutive first‐ever stroke survivors (46 men and 39 women; mean age 60.0 ± 12.4 years), who underwent 24‐h Holter monitoring before the beginning of a 60‐day rehabilitation program. Time‐domain measures of heart‐rate variability (HRV) were considered in all cases. By the end of the rehabilitation program an unfavorable functional outcome with dependency (Barthel Index score of <75) was found in 44.7% of patients. Multivariate analysis demonstrated that age odds ratio (OR) 1.09, 95% CI 1.04–1.19, P = 0.002, stroke severity (OR 1.12, 95% CI 1.01–1.34, P = 0.004), Barthel Index score (OR 0.92, 95% CI 0.87–0.98, P = 0.01) and Rankin Scale score (OR 3.88, 95% CI 2.13–7.56, P = 0.02) on admission, as well as lower values of the standard deviation of normal‐to‐normal R wave to R wave (RR) intervals (OR 9.67, 95% CI 2.58–18.67, P = 0.006) were independent predictors of an unfavorable functional outcome. Assessment of HRV before a rehabilitation program may provide additional information on the probability of a functional recovery in stroke survivors.
Histologic studies show that the amygdala is affected by Alzheimer disease (AD) pathology, and its medial aspect is the most involved. We aimed to assess in vivo local structural differences in the ...amygdala of patients with AD using high-field MRI.
A total of 19 patients with AD (mean age 76, SD 6 years, mean Mini-Mental State Examination score MMSE 13, SD 4) and 19 healthy elderly controls (age 74, SD 5, MMSE 29, SD 1) were enrolled. The radial atrophy mapping technique was used to reconstruct the 3-dimensional surface of the amygdala. Maps of surface tissue loss in patients with AD vs controls were computed and statistically tested with permutation tests thresholded at p < 0.05, to correct for multiple comparisons. A digital atlas of the amygdalar nuclei was used to infer which nuclei were involved.
Both amygdalar volumes were significantly smaller in patients with AD (right 1,508 mm³, SD 418; left 1,646, SD 419) than controls (right 2,129 mm³, SD 316; left 2,077, SD 376; p < 0.002). In the dorsomedial part, significant local tissue loss (20%-30%) was mapped in the medial and central nuclei. Ventrally, the lateral nucleus (La) and the basolateral ventral medial nucleus (BLVM) were also involved (20%-30% loss).
We found in vivo local structural differences in the amygdala of patients with AD. The nuclei involved have known connections to the hippocampus (BLVM, La) and olfactory system (medial nucleus) and with cholinergic pathways (central nucleus). This pattern is consistent with the known pathophysiology of neural systems affected by AD.
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